Departments of Pediatrics Psychiatry, Vanderbilt University, Nashville, TN, USA.
J Child Psychol Psychiatry. 2012 Feb;53(2):152-9. doi: 10.1111/j.1469-7610.2011.02455.x. Epub 2011 Aug 10.
Angelman syndrome (AS) is a neurogenetic disorder characterized by severe intellectual disability, lack of speech, and low threshold for laughter; it is considered a 'syndromic' form of autism spectrum disorder (ASD). Previous studies have indicated overlap of ASD and AS, primarily in individuals with larger (∼6 Mb) Class I deletions of chromosome 15q11-13. Questions remain regarding whether intellectual disability solely contributes to ASD features in AS and how ASD features in AS change over time. In this study, we used a dimensional approach to examine ASD symptom severity in individuals with AS Class I versus Class II deletions within the context of cognitive development over time.
A total of 17 participants with a larger, Class I deletion and 25 participants with a smaller Class II deletion (∼5 Mb) were enrolled (age range = 2-25 years; 5 years 5 months). Standardized measures of cognition, language, motor skills, adaptive skills, maladaptive behavior, autism, and sensory-seeking behaviors/aversions were given at baseline and after 12 months.
Despite equivalent cognition and adaptive behavior, the results of repeated measures analyses of variance indicate that participants with Class I deletions have greater impairment in social affect (F = 8.65; p = .006) and more repetitive behaviors (F = 7.92; p = .008) compared to participants with Class II deletions. Although both groups improve in cognition over time, differences in ASD behaviors persist.
Despite a lack of differences in cognition or adaptive behavior, individuals with Class I deletions have greater severity in ASD features and sensory aversions that remain over time. There are four genes (NIPA 1, NIPA 2, CYFIP1, and GCP5) missing in Class I and present in Class Il deletions, one or more of which may have a role in modifying the severity of social affect impairment, and level of restricted/repetitive behaviors in AS. Our results also suggest the utility of a dimensional, longitudinal approach to the assessment of ASD features in populations of individuals who are low functioning.
天使综合征（AS）是一种神经遗传疾病，其特征为严重的智力障碍、无语言能力和低笑点；它被认为是自闭症谱系障碍（ASD）的“综合征”形式。先前的研究表明，ASD 和 AS 存在重叠，主要见于染色体 15q11-13 较大（约 6 Mb）I 类缺失的个体。问题仍然是，智力障碍是否仅导致 AS 的 ASD 特征，以及 AS 中的 ASD 特征如何随时间变化。在这项研究中，我们使用维度方法，在随时间进行认知发展的背景下，研究 AS 中 I 类与 II 类缺失个体的 ASD 症状严重程度。
共纳入 17 名较大的 I 类缺失和 25 名较小的 II 类缺失（约 5 Mb）的参与者（年龄范围= 2-25 岁；5 岁 5 个月）。在基线和 12 个月后，给予认知、语言、运动技能、适应技能、适应不良行为、自闭症和感觉寻求行为/回避的标准化测量。
尽管认知和适应行为相当，但重复测量方差分析的结果表明，与 II 类缺失的参与者相比，I 类缺失的参与者在社会情感（F=8.65;p=0.006）和更重复行为（F=7.92;p=0.008）方面的损害更大。尽管两组认知随时间改善，但 ASD 行为的差异仍然存在。
尽管认知或适应行为无差异，但 I 类缺失的个体具有更严重的 ASD 特征和随时间持续的感觉回避。I 类缺失缺失而 II 类缺失存在的四个基因（NIPA1、NIPA2、CYFIP1 和 GCP5），其中一个或多个基因可能在改变社会情感损伤的严重程度和 AS 中受限/重复行为的水平方面发挥作用。我们的结果还表明，对于低功能人群，采用维度、纵向方法评估 ASD 特征是有用的。
